This renewal application requests funding for the 25th through 29th years of the NCI Cancer Center Support Grant of the City of Hope Comprehensive Cancer Center. The Center now has five research programs: one basic research Program (Cancer Biology, CB); three clinical/translational research Programs (Developmental Cancer Therapeutics, DCT; Cancer Immunotherapeutics, Cl; Hematologic Malignancies, HM); and one population research program (Cancer Control and Population Sciences, CCPS). Twelve shared resources support the scientific activities of the members, including two new cores (Small Animal Imaging; Clinical Immunobiology Correlative Studies Laboratory). Three developing cores are proposed (High Throughput Screening; Synthetic & Biopolymer Chemistry; Survey Research). Membership has grown by 45% in the preceding program period with the recruitment of 37 new Full Members, including several key senior leaders (Richard Jove, PhD, Deputy Director; R. Figlin, MD, Associate Director [AD] for Clinical Research). Other key leadership positions have also been filled through internal appointments (Smita Bhatia, MD, MPH, AD for Population Research; Joyce Niland, PhD, AD for Information Sciences; and Yun Yen, MD, PhD, AD for Translational Research). As a result of our program restructuring, recruitment and infrastructure development, we now believe we have a Center where our five Programs represent a continuum in which basic and translational studies in the basic science Program, CB, and one clinical Program, DCT, can be linked to Phase I and II clinical protocols in all three clinical programs (DCT, Cl, HM) and follow-up studies in survivorship and symptom management in the population sciences program (CCPS). All these activities are made possible by a Center and Institutional infrastructure that supports basic and translational research in biological and, now, small molecule approaches to cancer in an extraordinarily collaborative fashion. Such interaction has resulted in the Center's first SPORE, in lymphoma; a recent W.M. Keck Foundation award; and the renewal of eight large, multi-investigator awards. During the next funding period, we will build on these achievements so that the City of Hope Comprehensive Cancer Center takes the next step in its evolution: translating more laboratory discoveries into innovative clinical trials and developing disease-based research programs. The 82 Full Members and 90 Associate Members of the Center Programs have published 1001 articles, book chapters, etc., since the last competitive grant review. Of these, 28% are intraprogrammatic and 22% are interprogrammatic publications.